title: Deafferentation weakens excitatory synapses in the developing central auditory system.
abstract: Decreased excitatory synaptic activity during development often leads to pre- and postsynaptic atrophy, as assessed anatomically. The present study considers the effect of decreased excitatory transmission on the maturation of synaptic strength. Towards this end, cochlear nucleus neurons, which project to the ipsilateral lateral superior olive (LSO), were denervated in gerbils at postnatal day 7, before the onset of hearing. This manipulation was intended to disrupt spontaneous glutamatergic transmission in the LSO while sparing the glycinergic afferents from the medial nucleus of the trapezoid body (MNTB). Afferent-evoked synaptic activity was assessed 1-6 days after ablation in a brain slice preparation using whole-cell current- and voltage-clamp recordings. In control animals, ipsilaterally evoked excitatory postsynaptic potentials (EPSPs) were present in 91% of neurons tested, but were observed in only 60% of neurons following cochlea removal. The maximum EPSP amplitude was significantly smaller in manipulated neurons compared with controls, and this was accompanied by a higher incidence of ipsilaterally evoked inhibitory postsynaptic potentials (IPSPs). To study the efficacy of excitatory synapses in greater detail, voltage-clamp recordings were made in the presence of strychnine and AP-5 [D(O)-2-amino-5-phosphonopentanoic acid]. The minimum excitatory postsynaptic current (EPSC) amplitude, presumed to reflect the efficacy of a single glutamatergic afferent, was approximately 40% smaller in manipulated neurons. In contrast, MNTB-evoked IPSPs were similar in neurons from control and ablated animals. However, manipulated neurons often exhibited a rebound depolarization after a hyperpolarizing current pulse or an afferent-evoked IPSP. In 70% of manipulated neurons, synaptically evoked rebound depolarizations were reduced, but not eliminated, by glutamate receptor antagonists. The glycine receptor antagonist strychnine did eliminate the IPSP-associated depolarization in these neurons. Collectively, these results suggest that functional denervation of excitatory afferents decreases their synaptic efficacy as result of both cell loss as well as decreased strength of individual surviving synapses.
authors.affiliation: Center for Neural Science, New York University, New York 10003, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Kotak
authors.forename: D H
authors.initials: DH
authors.lastname: Sanes
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001933:Brain Stem / Q000254:growth & development / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D003051:Cochlea / Q000254:growth & development / Q000502:physiology; D017626:Cochlear Nucleus / Q000254:growth & development / Q000502:physiology*; D003714:Denervation; D004594:Electrophysiology; D018846:Excitatory Amino Acids / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D005849:Gerbillinae; D066298:In Vitro Techniques; D009475:Neurons, Afferent / Q000502:physiology*; D009847:Olivary Nucleus / Q000254:growth & development / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018846:Excitatory Amino Acids